Benzyl Alcohol → Ethyl 2-(benzyloxycarbonylamino)-1-(tert-butyldimethylsilyloxy)cyclopropanecarboxylate

Temperature

0 °C

A mixture of 2-(tert-butyldimethylsilyloxy)-2-(ethoxycarbonyl)cyclopropanecarboxylic acid (4b, 0.335 g, 1.16 mmol) in toluene (5 mL) under nitrogen was treated with Hünig's base (0.260 mL, 1.51 mmol) and the mixture was cooled to 0° C. After this time, DPPA (0.324 mL, 1.51 mmol) was added and the mixture was heated at 90° C. for 30 min, followed by the addition of benzyl alcohol (0.155 mL, 1.51 mmol). After 15 h, the mixture was cooled, diluted with ethyl acetate (75 mL), and washed sequentially with 10% citric acid (2×50 mL), water (50 mL), and saturated NaHCO3 (50 mL). The organic phase was dried (MgSO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 10% EtOAc/hexanes to 100% EtOAc to afford the title compound as a clear oil (0.146 g, 30%): 1H NMR (300 MHz, CDCl3) δ 7.34-7.30 (m, 5H), 5.40-5.38 (m, 1H), 5.21-5.00 (m, 2H), 4.29-4.18 (m, 2H), 4.16-4.09 (m, 1H), 1.50-1.47 (m, 2H), 1.30 (t, J=7.2 Hz, 3H), 0.88 (s, 9H), 0.26-0.07 (m, 6H); Multimode (APCI+ESI) MS m/z 295 [M+H]+.

1. temperaturethe mixture was heated at 90° C. for 30 min
2. temperaturethe mixture was cooled
3. washwashed sequentially with 10% citric acid (2×50 mL), water (50 mL), and saturated NaHCO3 (50 mL)
4. dry with materialThe organic phase was dried (MgSO4)
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by silica gel chromatography
8. washeluting with 10% EtOAc/hexanes to 100% EtOAc

ORD record

ord-927bed9bd55e4ad49de53205b531d5b1

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08481502B2